Stroke impairs neuro-vascular-glial function and causes sensorimotor impairments. Some degree of sensorimotor recovery subsequently occurs, yet the changes in neuro-vascular-glial function that are directly linked to this recovery are not well understood. Moreover, understanding and monitoring stroke recovery in humans using non-invasive imaging of cerebral hemodynamics [blood oxygenation level-dependent (BOLD);cerebral blood volume (CBV);cerebral blood flow (CBF)] is hampered by uncertainties about the relationship between neuro-vascular-glial unit signals and the recovery process. Our preliminary data, based on functional magnetic resonance imaging (fMRI) and optical imaging in an animal stroke model and fMRI in stroke patients, suggest a differential evolution in hemodynamic signals and the metabolic signal (cerebral metabolic rate of oxygen, CMRO2) during the period of sensorimotor recovery. The proposed project is aimed at characterizinisms that underlie the evolution in hemodynamic and metabolic changes during sensorimotor recovery. The proposed experiments in an animal stroke model and stroke patients are closely linked, and thereby will provide important insights into the evolution of stroke recovery on phenomenological and mechanistic levels. The results of this project will also identify non-invasive imaging biomarkers that correlate with underlying neuro-vascular-glial restoration and remodeling for use in monitoring stroke recovery and efficacy of potential therapeutic agents in patients.